Leigh disease

Leigh Disease

Leigh disease, also known as Leigh syndrome, is a rare, inherited neurodegenerative disorder that typically arises in infancy or early childhood. It is characterized by progressive loss of mental and movement abilities, and it often results in death within a few years, usually due to respiratory failure.

Pathophysiology

Leigh disease is a mitochondrial disorder, meaning it is caused by defects in the mitochondria, the energy-producing structures within cells. The condition is associated with mutations in nuclear DNA or mitochondrial DNA that affect the function of the mitochondria. These mutations lead to a disruption in the energy production process, particularly affecting the central nervous system.

The disease is named after Denis Leigh, who first described the condition in 1951. It is classified as a subacute necrotizing encephalomyelopathy, which refers to the characteristic lesions found in the brain, particularly in the basal ganglia, thalamus, brainstem, and spinal cord.

Clinical Presentation

Symptoms of Leigh disease typically begin in the first year of life, although later onset can occur. Common symptoms include:

• Developmental delay or regression
• Hypotonia (decreased muscle tone)
• Ataxia (lack of voluntary coordination of muscle movements)
• Seizures
• Ophthalmoplegia (paralysis or weakness of the eye muscles)
• Respiratory problems

The progression of symptoms is often rapid, and the disease can lead to severe disability and early death.

Diagnosis

Diagnosis of Leigh disease is based on clinical evaluation, imaging studies, and genetic testing. Magnetic resonance imaging (MRI) of the brain typically shows characteristic lesions in the affected areas. Genetic testing can identify mutations in the genes associated with the disease.

Genetic Basis

Leigh disease can be caused by mutations in over 75 different genes. These genes are involved in the production of proteins that are essential for mitochondrial function. The most common genetic causes include mutations in the SURF1 gene and mitochondrial DNA mutations such as those in the MT-ATP6 gene.

Inheritance patterns can vary depending on the specific genetic mutation. Leigh disease can be inherited in an autosomal recessive, X-linked, or mitochondrial pattern.

Treatment

There is currently no cure for Leigh disease, and treatment is primarily supportive and symptomatic. Management may include:

• Nutritional support
• Physical therapy
• Medications to manage symptoms such as seizures
• Respiratory support

Some patients may benefit from specific dietary supplements, such as thiamine or coenzyme Q10, although the effectiveness of these treatments can vary.

Prognosis

The prognosis for individuals with Leigh disease is generally poor, with most affected children not surviving beyond a few years after the onset of symptoms. However, the course of the disease can vary depending on the specific genetic mutation and the severity of the symptoms.

Also see

• Mitochondrial disease
• Neurological disorder
• Genetic disorder
• Basal ganglia disease

Classification
External resources